In a nutshell
The authors evaluated the effectiveness of combination therapy of dabrafenib (Tafinlar) and trametinib (Mekinist) in advanced melanoma patients with mutations (permanent changes) in BRAF genes. The authors found out that the combination therapy improved overall survival (time from treatment until death from any cause).
Some background
In advanced melanoma (stage 3 or 4), cancer spreads from the skin to other parts of the body. Targeted therapy has shown improved outcomes in these stages of the disease. Targeted therapies block specific genes, such as BRAF, that are often mutated in melanoma patients.
BRAF inhibitors such as dabrafenib block certain proteins in BRAF-mutated melanoma cells. BRAF inhibitors have led to significant improvements in the treatment of melanoma. However, patients can become resistant to BRAF inhibitors. It is thought that a combination of therapies that inhibit different proteins may be more effective than one inhibitor alone. Trametinib, for example, blocks a different protein than dabrafenib. These treatments may be more effective when used together.
Methods & findings
The authors compared the effectiveness of dabrafenib and trametinib to that of dabrafenib alone in advanced melanoma.
423 patients were included in this trial. All patients had advanced melanoma that could not be surgically removed. None of the patients had been treated previously. 211 patients in group 1 received combination of dabrafenib and trametinib. 212 patients in group 2 received dabrafenib and placebo (substance with no effect on the body). Patients were followed for close to 3 years.
The average overall survival in group 1 was 25.1 months and 18.7 months in group 2. The 1-year overall survival rate was 74% for group 1 and 68% for group 2. Average 2-year overall survival was 51% for group 1 and 42% for group 2.
The average progression-free survival (time following treatment before the disease progressed) was significantly longer in group 1 (11 months) compared to group 2 (8.8 months).
The most common treatment-related side effect in group 1 was fever. In group 2 patients, it was thickening of outer layer of the skin. 32% of patients in group 1 and 31% of group 2 had severe or life-threatening side-effects.
The bottom line
The authors concluded that the combination therapy of dabrafenib and trametinib improved overall survival in advanced melanoma patients.
Published By :
The Lancet
Date :
May 29, 2015
